Next-Generation Sequencing (NGS) technologies provide a key mechanism in the expansion of precision medicine, wherein treatments are designed based on the genetics unique to an individual patient's illness. A long-standing and effective application of this concept has been in the clinical arena of hematopoietic cell transplants (HCTs), where for over 30 years genetic information has been used in curing lymphoid and myeloid malignancies. Primarily through genotyping of HLA loci and matching genotypes between donor and recipient, clinical immunogenetics laboratories (CILs) have played an essential role in the treatment of these diseases. In this capacity, NGS has an immediate application in CILs supporting HCTs. There are currently over 190 HLA typing laboratories accredited by the American Society of Histocompatibility and Immunogenetics (ASHI). Most of these laboratories support transplant programs that collectively perform thousands of HCTs each year worldwide. Additionally, the resolution of HLA typing data has dramatically improved due to technological advances and reference data sets contributed by CILs, and the resultant improved matching is strongly correlated with improved outcomes. Due to the costs of traditional genotyping methods, CILs must adopt an NGS-based approach in order to contribute among large companies that perform high-throughput HLA typing services. During the past three years, Scisco Genetics Inc. and the Fred Hutchinson Cancer Research Center (FHCRC) have collaborated to build an NGS workflow supported by an informatics infrastructure that can thusly enable clinical laboratories genotyping human immune response genes. Our Integrated Genotyping System (IGS) is a comprehensive solution comprising workflows with detailed procedures, reagents, and data analysis software. The system is configured with our Genetics Management System (GeMS) informatics framework, which includes the software tools necessary for ASHI-compliant personnel, reagent and sample tracking and data analysis and reporting. The IGS has proven to be effective in reducing costs by enabling our partner CILs to replace their current multifold approach - involving an ensemble of low-, mid-, and high- resolution HLA typing methods - with a single NGS workflow. This reduction of operating costs is accompanied by an increase in HLA data quality and precision. Also, with the IGS, CILs will be able to seamlessly incorporate new genetic tests exploring the intersection of genetics and immunity. Accordingly, we propose to achieve the following specific aims: (1) To disseminate the Scisco Genetics Inc. Integrated Genotyping System (IGS) to targeted Clinical Immunogenetics Laboratories, while gathering data on innovative new genetic approaches applicable to HCTs; (2) To improve and expand functionality for other genetic systems routinely tested in CILs and to enable new genotyping strategies in support of clinical research. Several key pieces of our product are now available and ready for deployment, but require capital and intellectual investment to help transition CILs to the routine use of the product workflows. Scisco is now working with three CILs to install the IGS providing a model for furthering aim 1 and suggesting directions for future developments within aim 2.